The cornea functions as the main refractive element of the visual system, contributing between 65-75 percent of the eye's total focusing power. Proper refraction of light depends on the smooth surface and transparency of the cornea and diseases affecting the cornea are a major cause of blindness worldwide. To understand the pathological consequences and develop appropriate treatment protocols for corneal diseases, it is important to elucidate the pathways underlying the normal maintenance of corneal integrity and function, and the molecular mechanisms causing abnormalities. Animal models for corneal diseases provide useful experimental systems for these purposes. Mice homozygous for the autosomal recessive corneal disease-1 (corn1) mutation develop a roughened, opaque corneal surface caused by hyperproliferation, and subsequent corneal neovascularization. We previously determined that deletion of destrin (Dstn), a major regulator of actin dynamics, is responsible for these corneal abnormalities. The long-term goal of this research is to determine the role proper regulation of actin dynamics play in the cornea. Our subsequent analyses of the mutant identified a series of gene expression changes downstream of the Dstn mutation and actin dynamics defects, which may underlie epithelial hyperproliferation and neovascularization in the cornea, and also the finding that the Dstn-corn1 mutation leads to an auto-inflammatory condition in the cornea. This information now allows us to build new hypotheses on the molecular pathways responsible for the corneal phenotypes in Dstn-corn1 mice, which we propose to test in this renewal application. Specifically, we propose to (1) test whether defects in actin dynamics lead to corneal abnormalities through transcription factor dependent pathways in Dstn-corn1 mice and (2) determine the role inflammatory cells and molecules play in the development of corneal abnormalities observed in Dstn-corn1 mice.